Skip to main content
Log in

Relationship between injury-induced astrogliosis, laminin expression and axonal sprouting in the adult rat brain

  • Published:
Journal of Neurocytology

Summary

Lesion-induced regenerative sprouting of CNS axons is accompanied by structural and metabolic changes of astrocytes. In order to evaluate the effects of these astrocytic changes on axonal regeneration, we investigated the spatio-temporal relationship of gliosis, laminin expression and axonal sprouting in the postcommissural fornix of the adult rat. Using immunocytochemical methods we observed (1) a perilesional area with a transient lack of astrocytes and axons, (2) the reappearance of reactive astrocytes followed by the ingrowth of sprouting fibres and finally an increase in laminin-immunoreactivity, (3) the absence of lesion-induced laminin-expression in reactive astrocytes and (4) the formation and long-lasting (at least 28 months) persistence of a dense plexus of laminin-immunopositive blood vessels at the site of transection and in the proximal and distal stumps. These data indicate that astrogliosis is permeable for regrowing axons and that injury-induced axonal sprouting in the transected postcommissural fornix may be mediated by laminin-independent mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alonso, G. &Privat, A. (1993a) Neuropeptide Y-producing neurons of the arcuate nucleus regenerate axons after surgical deafferentiation of the mediobasal hypothalamus.Journal of Neuroscience Research 34, 510–22.

    PubMed  Google Scholar 

  • Alonso, G. &Privat, A. (1993b) Reactive astrocytes involved in the formation of lesional scars differ in the mediobasal hypothalamus and in other forebrain regions.Journal of Neuroscience Research 34, 523–38.

    PubMed  Google Scholar 

  • Ard, M. D. &Bunge, R. P. (1986) Tissue culture observations on the interactions of astrocytes, extracellular matrix and neurites.Society for Neuroscience Abstracts 12, 395.

    Google Scholar 

  • Ard, M. D. &Faissner, A. (1991) Components of astrocytic extracellular matrix are regulated by contact with axons.Annals of the New York Academy of Sciences 633, 566–9.

    PubMed  Google Scholar 

  • Bähr, M. (1991) Adult rat retinal gliain vitro: effects ofin vivo crush-activation on glia proliferation and permissiveness for regenerating retinal ganglion cell axons.Experimental Neurology 111, 65–73.

    PubMed  Google Scholar 

  • Bernstein, J. J. &Bernstein, M. E. (1971) Axonal regeneration and formation of synapses proximal to the site of lesion following hemisection of the rat spinal cord.Experimental Neurology 30, 336–51.

    PubMed  Google Scholar 

  • Bernstein, J. J., Getz, R., Jefferson, M. &Kelemen, M. (1985) Astrocytes secrete basal lamina after hemisection of rat spinal cord.Brain Research 327, 135–41.

    PubMed  Google Scholar 

  • Berry, M., Hall, S., Follows, R., Rees, L., Gregson, N. &Sievers, J. (1988) Response of axons and glia at the site of anastomosis between the optic nerve and cellular and acellular sciatic nerve grafts.Journal of Neurocytology 17, 727–44.

    PubMed  Google Scholar 

  • Berry, M., Hall, S., Rees, L., Carlile, J. &Wyse, J. P. H. (1992) Regeneration of axons in the optic nerve of the adult Browman-Wyse (BW) mutant rat.Journal of Neurocytology 21, 426–48.

    PubMed  Google Scholar 

  • Björklund, A., Katzman, R., Stenevi, U. &West, K. A. (1971) Development and growth of axonal sprouts from noradrenalin and 5-hydroxytryptamine neurones in the rat spinal cord.Brain Research 31, 21–33.

    PubMed  Google Scholar 

  • Björklund, A. &Stenevi, U. (1979) Regeneration of monoaminergic and cholinergic neurons in the central nervous system.Physiological Reviews 59, 62–100.

    PubMed  Google Scholar 

  • Blaugrund, E., Duvdevani, R., Lavie, V., Solomon, A. &Schwartz, M. (1992) Disappearance of astrocytes and invasion of macrophages following crush injury of adult rodent optic nerves: implications for regeneration.Experimental Neurology 118, 105–15.

    PubMed  Google Scholar 

  • Blaugrund, E., Lavie, V., Cohen, I., Solomon, A., Schreyer, D. J. &Schwartz, M. (1993) Axonal regeneration is associated with glial migration: comparison between the injured optic nerves of fish and rats.Journal of Comparative Neurology 330, 105–12.

    PubMed  Google Scholar 

  • Bovolenta, P., Wandosell, F. &Nieto-Sampedro, M. (1993) Characterization of neurite outgrowth inhibitor expressed after CNS injury.European Journal of Neuroscience 5, 454–65.

    PubMed  Google Scholar 

  • Carlstedt, T. (1985) Regenerating axons form nerve terminals at astrocytes.Brain Research 347, 188–91.

    PubMed  Google Scholar 

  • Cheng, C. T., Zhou, F. C. &Lee, C. H. (1989) Laminin expression in developmental rat brain: a quantitativein situ hybridization study using image analyzer.Society for Neuroscience Abstracts 15, 278.

    Google Scholar 

  • Clemente, C. D. (1955) Structural regeneration in the mammalian central nervous system and the role of neuroglia and connective tissue. In:Regeneration in the Central Nervous System (edited byWindle, W. F.) pp. 147–61. Springfield, IL: Charles C. Thomas.

    Google Scholar 

  • Cohen, J., Burne, J. F., Winter, J. &Bartlett, P. (1986) Retinal ganglion cells lose response to laminin with maturation.Nature 322, 465–7.

    PubMed  Google Scholar 

  • David, S. (1988) Neurite outgrowth from mammalian CNS neurons on astrocytes in vitro may not be mediated primarily by laminin.Journal of Neurocytology 17, 131–44.

    PubMed  Google Scholar 

  • David, S., Bouchard, C., Tsatas, O. &Giftochristos, N. (1990) Macrophages can modify the nonpermissive nature of the adult mammalian central nervous system.Neuron 5, 463–9.

    PubMed  Google Scholar 

  • Dellmann, H. D. (1973) Degeneration and regeneration of neurosecretory systems.International Reviews of Cytology 36, 215–315.

    Google Scholar 

  • Eddleston, M. &Mucke, L. (1993) Molecular profile of reactive astrocytes — implications for their role in neurological disease.Neuroscience 54, 15–36.

    PubMed  Google Scholar 

  • Edgar, D., Timpl, R. &Thoenen, H. (1984) The heparinbinding domain of laminin is responsible for its effects on neurite outgrowth and neuronal survival.EMBO Journal 3, 1463–8.

    PubMed  Google Scholar 

  • Engvall, E., Davis, G. E., Dickerson, K., Ruoslahti, E., Varon, S. &Manthorpe, M. (1986) Mapping of domains in human laminin using monoclonal antibodies: localization of neurite-promoting site.Journal of Cell Biology 103, 2457–65.

    PubMed  Google Scholar 

  • Eriksdotter-Nilsson, M., Björklund, H. &Olson, L. (1986) Laminin immunohistochemistry: a simple method to visualize and quantitate vascular structures in the mammalian brain.Journal of Neuroscience Methods 17, 275–86.

    PubMed  Google Scholar 

  • Eriksdotter-Nilsson, M., Björklund, H., Dahl, D., Olson, L. &Ingvar, M. (1987) Sustained seizures cause circumscribed cerebral changes in glial fibrillary acidic protein, neurofilament and laminin immunofluorescence.Experimental Brain Research 69, 155–66.

    Google Scholar 

  • Fawcett, J. W. (1989) Oligodendrocytes repel axons and cause axonal growth cone collapse.Journal of Cell Science 92, 93–100.

    PubMed  Google Scholar 

  • Feringa, E. R., Kowalski, T. F. &Vahlsing, H. L. (1980) Basal lamina formation at the site of spinal cord transection.Annals of Neurology 8, 148–54.

    PubMed  Google Scholar 

  • Fernaud-Espinosa, I., Nieto-Sampedro, M. &Bovolenta, P. (1993) Differential activation of microglia and astocytes in aniso- and isomorphic gliotic tissue.Glia 8, 277–91.

    PubMed  Google Scholar 

  • Frisen, J., Fried, K., Sjögren, M. &Risling, M. (1993) Growth of ascending spinal axons in CNS scar tissue.International Journal of Developmental Neuroscience 11, 461–75.

    PubMed  Google Scholar 

  • Gasser, U. E. &Hatten, M. E. (1990) Neuron-glia interactions of developing rat hippocampal cellsin vitro: glial-guided neuronal migration and neuronal regulation of glial differentiation.Journal of Neuroscience 10, 1276–85.

    PubMed  Google Scholar 

  • Giftochristos, N. &David, S. (1988) Laminin and heparan sulphate proteoglycan in the lesioned adult mammalian central nervous system and their possible relationship to axonal sprouting.Journal of Neurocytology 17, 385–97.

    PubMed  Google Scholar 

  • Gocht, A. &Löhler, J. (1993) Microenvironmental changes during axonal regrowth in the optic nerve of the myelin deficient rat. Immunocytochemical and ultrastructural observations.Journal of Neurocytology 22, 461–79.

    PubMed  Google Scholar 

  • Grabber, M. B., Streit, W. J. &Kreutzberg, G. W. (1988) The microglial cytoskeleton: vimentin is localized within activated cellsin situ.Journal of Neurocytology 17, 573–80.

    PubMed  Google Scholar 

  • Graziadei, P. P. D. &Monti Graziadei, G. A. (1978) The olfactory system: a model for the study of neurogenesis and axon regeneration in mammals. In:Neuronal Plasticity (edited byCotman, C. W.) pp. 113–53. New York: Raven Press.

    Google Scholar 

  • Hagg, T., Muir, D., Engvall, E., Varon, S. &Manthorpe, M. (1989) Laminin-like antigen in rat CNS neurons: distribution and changes upon brain injury and nerve growth factor treatment.Neuron 3, 721–32.

    PubMed  Google Scholar 

  • Hall, S., Gregson, N. &Rickard, S. (1991) Interaction of regrowing PNS axons with transplanted aggregates of cultured CNS gliain vivo.Journal of Neurocytology 20, 299–309.

    PubMed  Google Scholar 

  • Hatten, M. E. (1985) Neuronal regulation of astroglial morphology and proliferation in vitro.Journal of Cell Biology 100, 384–96.

    PubMed  Google Scholar 

  • Hatten, M. E., Liem, R. K. H., Shelanski, M. L. &Mason, C. A. (1991) Astroglia in CNS injury.Glia 4, 233–43.

    PubMed  Google Scholar 

  • Hausmann, B., Sievers, J., Hermanns, J. &Berry, M. (1989) Regeneration of axons from the adult rat optic nerve: influence of fetal brain grafts, laminin and artificial basement membrane.Journal of Comparative Neurology 281, 447–66.

    PubMed  Google Scholar 

  • Hu, C. T., Zhou, F. C., Hwang, Y. W. &Lee, C. H. (1988) Laminin expression in the developmental rat brain: an immunocytochemical andin situ-hybridization study.Society for Neuroscience Abstracts 14, 364.

    Google Scholar 

  • Hunter, D. D., Llinas, R., Ard, M., Merlie, J. P. &Sanes, J. R. (1992) Expression of S-laminin and laminin in the developing rat central nervous system.Journal of Comparative Neurology 323, 238–51.

    PubMed  Google Scholar 

  • Jucker, M., Kleinman, H. K., Höhmann, C. F., Ordy, J. M. &Ingram, D. K. (1991) Distinct immunoreactivity to 110 kDa laminin-binding protein in adult and lesioned rat forebrain.Brain Research 555, 305–12.

    PubMed  Google Scholar 

  • Jucker, M., Bialobok, P., Hagg, T. &Ingram, D. K. (1992) Laminin immunohistochemistry in brain is dependent on method of tissue fixation.Brain Research 586, 166–70.

    PubMed  Google Scholar 

  • Kao, C. C., Chang, L. W. &Bloodworth, J. M. B.Jr. (1977) Axonal regeneration across transected mammalian spinal cords: an electron microscopic study of delayed microsurgical nerve grafting.Experimental Neurology 54, 591–615.

    PubMed  Google Scholar 

  • Kawaja, M. D., Rosenberg, M. B., Yoshida, K., Friedman, T. &Gage, F. H. (1990) Axonal sprouting induced by striatal implants of genetically modified fibroblasts that produce nerve growth factor.Society for Neuroscience Abstracts 16, 814.340.4

    Google Scholar 

  • Kiernan, J. A. (1979) Hypotheses concerned with axonal regeneration in the mammalian nervous system.Biological Reviews 54, 155–97.

    PubMed  Google Scholar 

  • Kleinman, H. K., McGarvey, M. L., Liotta, L. A., Robey, P. G., Tryaason, K. &Martin, G. R. (1985) Isolation and characterization of type IV procollagen, laminin and heparan sulfate proteoglycan from the EHS sarcoma.Biochemistry 21, 6188–93.

    Google Scholar 

  • Lawrence, J. M., Huang, S. K. &Raisman, G. (1984) Vascular and astrocytic reactions during establishment of hippocampal transplants in adult host brain.Neuroscience 12, 745–60.

    PubMed  Google Scholar 

  • Laywell, E. D., Dörries, U., Bartsch, U., Faissner, A. &Schachner, M. (1992) Enhanced expression of the developmentally regulated extracellular matrix molecule tenascin following adult brain injury.Proceedings of the National Academy of Sciences (USA) 89, 2634–8.

    Google Scholar 

  • Liesi, P. (1985) Laminin-immunoreactive glia distinguish regenerative adult CNS systems from non-regenerating ones.EMBO Journal 4, 2505–11.

    PubMed  Google Scholar 

  • Liesi, P., Kaakkola, S., Dahl, D. &Vaheri, A. (1984) Laminin is produced in astrocytes of adult brain by injury.EMBO Journal 3, 683–6.

    PubMed  Google Scholar 

  • Liuzzi, F. J. &Lasek, R. J. (1987) Astrocytes block axonal regeneration by activating the physiological stop pathway.Science 237, 642–64.

    PubMed  Google Scholar 

  • Mansour, H., Asher, R., Dahl, D., Labkovsky, B., Perides, G. &Bignami, A. (1990) Permissive and nonpermissive reactive astrocytes: immunofluorescence study with antibodies to the glial hyaluronate-binding protein.Journal of Neuroscience Research 25, 300–11.

    PubMed  Google Scholar 

  • Manthorpe, M., Engvall, E., Ruoslahti, E., Longo, F. M., Dans, G. E. &Varon, S. (1983) Laminin promotes neuritic regeneration from cultured peripheral and central neurons.Journal of Cell Biology 97, 1882–90.

    PubMed  Google Scholar 

  • Matthiessen, H. P., Schmalenbach, C. &Müller, H. W. (1989) Astroglia-released neurite growth inducing activity for embryonic hippocampal neurons is associated with laminin bound in a sulfated complex and free fibronectin.Glia 2, 177–88.

    PubMed  Google Scholar 

  • McKeon, R. J., Schreiber, R. C., Rudge, J. S. &Silver, J. (1991) Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes.Journal of Neuroscience 11, 3398–411.

    PubMed  Google Scholar 

  • McLean, I. W. &Nakane, P. K. (1974) Periodate-lysineparaformaldehyde fixative. A new fixative for immunelectron microscopy.Journal of Histochemistry and Cytochemistry 22, 1077–83.

    Google Scholar 

  • McLoon, S. C. (1986) Response of astrocytes in the visual system to Wallerian degeneration: an immunohistochemical analysis of laminin and glial fibrillary acidic protein (GFAP).Experimental Neurology 91, 613–21.

    PubMed  Google Scholar 

  • Neuberger, T. J., Cornbrooks, C. J. &Kromer, L. F. (1992) Effects of delayed transplantation of cultured Schwann cells on axonal regeneration of central nervous system cholinergic neurons.Journal of Comparative Neurology 315, 16–33.

    PubMed  Google Scholar 

  • Ogawa, M., Araki, M., Nagatsu, I. &Yoshida, M. (1989) Astroglial cell alteration caused by neurotoxins: immunohistochemical observations with antibodies to glial fibrillary acidic protein, laminin and tyrosine hydroxylase.Experimental Neurology 106, 187–96.

    PubMed  Google Scholar 

  • Pindzola, R. R., Doller, C. &Silver, J. (1993) Putative inhibitory extracellular matrix molecules at the dorsal root entry zone of the spinal cord during development and after root and sciatic nerve lesions.Developmental Biology 156, 34–48.

    PubMed  Google Scholar 

  • Rakic, P. (1981) Neuronal-glial interaction during brain development.Trends in Neurosciences 4, 184–7.

    Google Scholar 

  • Ramon Ycajal, S. (1928)Degeneration and Regeneration of the Nervous System. New York: Hafner.

    Google Scholar 

  • Reier, P. J. &Houle, J. D. (1988) The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair. In:Advances in Neurology: Functional Recovery of Neurological Disease, (edited byWaxman, S. G.) pp. 87–138. New York: Raven Press.

    Google Scholar 

  • Reier, P. J., Stensaas, L. J. &Guth, L. (1983) The astrocytic scar as an impediment to regeneration in the central nervous system. In:Spinal Cord Reconstruction (edited byKao, C. C., Bunge, R. P. &Reier, P. J.) Vol. 47. pp. 163–96. New York: Raven Press.

    Google Scholar 

  • Rogers, S. L., Letourneau, P. C., Palm, S. L., McCarthy, J. &Furcht, L. T. (1983) Neurite extension by peripheral and central nervous system neurons in response to substratum-bound fibronectin and laminin.Developmental Biology 98, 212–20.

    PubMed  Google Scholar 

  • Rudge, J. S. &Silver, J. (1990) Inhibition of neurite outgrowth on astroglial scarsin vitro.Journal of Neuroscience 10, 3594–603.

    PubMed  Google Scholar 

  • Schiffer, D. E., Giordana, M. T., Giaccone, G., Pezzotta, S. &Mauro, A. (1986) Glial fibrillary acidic protein and vimentin in the experimental glial reaction of the rat brain.Brain Research 374, 110–18.

    PubMed  Google Scholar 

  • Schmidt-Kastner, R., Wietasch, K., Weigel, H. &Eysel, U. T. (1993) Immunohistochemical staining for glial fibrillary acidic protein (GFAP) after deafferentiation or ischemic infarction in rat visual system: features of reactive and damaged astrocytes.International Journal of Developmental Neuroscience 11, 157–74.

    PubMed  Google Scholar 

  • Schwab, M. E. &Caroni, P. (1988) Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreadingin vitro.Journal of Neuroscience 8, 2381–93.

    PubMed  Google Scholar 

  • Schwab, M. E., Kapfhammer, J. P. &Bandtlow, C. E. (1993) Inhibitors of neurite growth.Annual Reviews of Neuroscience 16, 565–95.

    Google Scholar 

  • Shigematsu, K., Kamo, H., Akiguchi, I., Kimura, J., Kameyama, M. &Kimura, H. (1989) Neovascularization in kainic acid-induced lesions of rat striatum: an immunohistochemical study with laminin.Brain Research 501, 215–22.

    PubMed  Google Scholar 

  • Smith, G. M., Rutishauser, U., Silver, J. &Miller, R. H. (1986) Changing role of forebrain astrocytes during development, regenerative failure, and induced regeneration upon transplantation.Journal of Comparative Neurology 251, 23–43.

    PubMed  Google Scholar 

  • Sosale, A., Robson, J. A. &Stelzner, D. J. (1988) Laminin distribution during corticospinal tract development and after spinal cord injury.Experimental Neurology 102, 14–22.

    PubMed  Google Scholar 

  • Stichel, C. C., Singer, W. &Zilles, K. (1990) Ultrastructure of PkC (II/III)-immunopositive structures in rat primary visual cortex.Experimental Brain Research 82, 575–84.

    Google Scholar 

  • Stichel, C. C. &Müller, H. W. (1994) Extensive and long-lasting changes of glial cells following transection of the postcommissural fornix in the adult rat.Glia 10, 89–100.

    PubMed  Google Scholar 

  • Suzuki, H., Yamamoto, T., Yamamoto, H., Konno, H., Iwasaki, Y., Ohara, Y. &Terunuma, H. (1990) Intraneuronal laminin-like immunoreactivity in the human central nervous system.Brain Research 520, 324–9.

    PubMed  Google Scholar 

  • Takamiya, Y., Kohsaka, S., Toya, S., Otani, M. &Tsukada, Y. (1988) Immunohistochemical studies on the proliferation of reactive astrocytes and the expression of cytoskeletal proteins following brain injury in rats.Developmental Brain Research 38, 201–10.

    Google Scholar 

  • Timple, R., Rohde, H., Robey, P. G., Rennard, S. I., Foidart, J.-M. &Martin, G. R. (1979) Laminin — a glycoprotein from basement membranes.Journal of Biological Chemistry 254, 9933–7.

    PubMed  Google Scholar 

  • Tomaselli, K. J., Reichardt, L. F. &Bixby, J. L. (1986) Distinct molecular interactions mediate neuronal process outgrowth on non-neuronal cell surfaces and extracellular matrices.Journal of Cell Biology 103, 2659–72.

    PubMed  Google Scholar 

  • Wilkin, G. P., Marriott, D. R. &Cholewinski, A. J. (1990) Astrocyte heterogeneity.Trends in Neuroscience 13, 43–6.

    Google Scholar 

  • Wolburg, H. &Kästner, R. (1984) Is the architecture of astrocytic membrane crucial for axonal regeneration in the central nervous system?Naturwissenschaften 71, 484–5.

    PubMed  Google Scholar 

  • Wujek, J. R. &Reier, P. J. (1984) Astrocytic membrane morphology: differences between mammalian and amphibian astrocytes after axotomy.Journal of Comparative Neurology 222, 607–19.

    PubMed  Google Scholar 

  • Wunderlich, G., Stichel, C. C., Schroeder, W. &Müller, H. W. (1994) Transplants of immature astrocytes promote axonal regeneration in the adult rat brain.Glia 10, 49–58.

    PubMed  Google Scholar 

  • Yamamoto, T., Iwasaki, Y., Yamamoto, H., Konno, H. &Isemura, M. (1988) Intraneuronal laminin-like molecule in the central nervous system: demonstration of its unique differential distribution.Journal of the Neurological Sciences 84, 1–13.

    PubMed  Google Scholar 

  • Zhou, F. C. (1990) Four patterns of laminin-immunoreactive structure in developing rat brain.Developmental Brain Research 55, 191–201.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stichel, C.C., Müller, H.W. Relationship between injury-induced astrogliosis, laminin expression and axonal sprouting in the adult rat brain. J Neurocytol 23, 615–630 (1994). https://doi.org/10.1007/BF01191556

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01191556

Keywords

Navigation